This is a re-submission in response to program announcement PAR-06-172. The Principal Investigator (Marney A. White, Ph.D.) is currently in the third year of a K23 Mentored Patient-Oriented Research Career Development Award (K23-DK071646) from NIDDK. One of the studies proposed in the K23 is a placebo-controlled randomized clinical trial of bupropion for the treatment of overweight women with binge eating disorder (BED). The proposed study seeks to increase enrollment of the now active bupropion RCT in order to specifically investigate treatment outcomes for women with and without a history of cigarette smoking. A programmatic series of studies - supported by the K23 - has found important differences between former smokers and never smokers with BED in terms of clinical presentation. Compared to never smokers, women with a smoking history are more likely to have comorbid psychological problems, and are more likely to report specific symptoms of eating pathology (e.g., rigid dieting strategies). Preliminary research described in this application has found that for former smokers, food cravings are related to overeating in response to negative emotions, whereas no such relationship is observed among never smokers. Furthermore, secondary analyses of completed RCTs of psychological treatments for BED (conducted at Yale) suggest different mechanisms of treatment response between former and never smokers. For women with a smoking history, the degree of improvement in response to psychological treatment for BED is related to reductions in food cravings and negative emotional eating. Since bupropion is theorized to reduce cravings and negative mood, it may be a particularly effective pharmacological agent for former smokers with BED;i.e., smoking history may be a moderator of response to bupropion. The proposed study has the potential to inform our understanding of underlying mechanisms and maintaining factors in binge eating, and to improve treatments. Results from the proposed study are expected to inform the development of a larger-scale RCT for disordered eating and obesity. PUBLIC HEALTH RELEVANCE: The current study seeks to test the effectiveness of bupropion for the treatment of binge eating among overweight women. Bupropion is a FDA-approved medication for treating depression and for smoking cessation, and is theorized to reduce cravings and negative mood. Because the nature of binge eating may differ as a function of smoking history, the current study also seeks to determine whether women with a history of cigarette smoking will show greater improvements than women with binge eating problems who have never smoked.